Science —

Infinite chicken wings?

What new results don't tell us about regeneration of vertebrate limbs.

Those readers who also pay attention to Slashdot might have noted a story about regeneration of chicken wings. It's always tough to know what to do when a science story appears at Slashdot. Their story summaries are so brief that they say nearly nothing about the actual findings, leaving a lot of room for the sort of explanation we here at Nobel Intent strive for. At the same time, if it's on Slashdot, the story is probably overexposed, and there's always the chance that somewhere among the jokes and ironic asides in the comments, someone has actually explained the science. Three factors, however, have encouraged me to cover this story: Slashdot's comments contain little beyond jokes about infinite buffalo wings; I know vertebrate limb development quite well; and, most significantly, the story's absolute rubbish.

The problems presumably start with a press release, which contains the statement that a new paper demonstrates that scientists have, "been able to regenerate a wing in a chick embryo—a species not known to be able to regrow limbs—suggesting that the potential for such regeneration exists innately in all vertebrates, including humans." I don't think the paper itself does anything of the sort, nor does it claim to. The whole problem seems to arise from people being incapable of realizing that there are important differences between embryonic development and regeneration after embryonic development is over.

The confusion arises because there are similarities between the two processes. During embryonic development, a structure called the AER forms at the tip of the nascent limb and produces signaling molecules that help direct the outgrowth of the limb. Classical experiments dating from the 1950s showed that in chickens, if you cut off the AER shortly after the limb starts growing, the limb truncates at the first long bone, the humerus. Cut it off later, and you get more limb. We've known for nearly a decade that the formation of the AER can be triggered by members of a protein family called the Wnts.

Meanwhile, there are some vertebrates, such as fish and amphibians, that can regenerate damaged limbs/fins as adults. To an extent, this process seems to involve recruiting some cells that act like embryonic limb cells, and reproducing the embryonic process. A structure similar to the AER forms during regeneration, and the paper in question shows that Wnt signaling is also needed for the regeneration process. Block the Wnts, and the regeneration fails. This reinforces the sense that the two processes share some significant parallels. It also suggests that if we're ever to regenerate human limbs, there's a good chance that Wnts will be a key part of the process. It's all good.

But the authors also do a somewhat odd experiment, the one that led to all the problems. They worked in chickens (which can't regenerate as adults), and showed that if you chopped the AER off early in limb development and activated the Wnt signaling pathway at the same time, the AER reformed, and limb development partially recovered. This really only shows that you can regenerate an AER, which can only do something useful if there's the appropriate limb-forming tissue nearby. If there wasn't a developing limb in place, the ability to form this AER would be meaningless. The AER was also regenerated from the same tissue that formed it in the first place, about a day after it normally forms.

In technical language, the paper showed that limb tissue remains competent to form an AER for over 24 hours after AER formation is normally complete. It's not very surprising, but it's not clear what it tells us, either. But it is clear that this is a VERY different finding from one showing that birds (and, by extension, other tetrapods) have a nascent limb regeneration system, just waiting to be triggered. Making that illogical leap is borderline irresponsible.

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